The major goals of the Neuro-Oncology (NRO) Program are to understand the molecular mechanisms that are involved in the etiopathogenesis and progression of primary brain tumors and metastases to brain, and to use this knowledge to better manage patients with these malignancies; they belong to a high incidence/high mortality population in the Wake Forest Baptist Comprehensive Cancer Center (WFBCCC) catchment area. The mission of the Program is to develop a comprehensive initiative that yields significant improvements in the management of patients with primary brain tumors and metastases to the brain. This will be achieved by the Program members? research around three aims: 1) cancer stem-like cells (mechanisms regulating participation of these cells in cancer initiation and progression, and those that are potential targets for therapeutics), 2) novel approaches to treatment (identifying new therapeutic strategies including those that lead to improved delivery of drugs to the CNS), and 3) clinical investigations (leverages the rich history of early phase clinical brain tumor research at the WFBCCC through long-standing participation in the Adult Brain Tumor Consortium (ABTC), other national brain tumor collaborations, as well as investigator-initiated trials). The research of the NRO Program focuses particularly on malignant gliomas, including glioblastoma, and breast and lung cancer brain metastases. More specifically, the Program?s Specific Aims are addressed as follows: Aim 1 is to determine the role of cancer stem-like cells in tumor initiation and/or progression through studying signaling pathways and interactions with other cell types present in the tumor microenvironment and normal brain; Aim 2 is to develop novel devices, techniques, drug candidates and therapeutic approaches for these difficult-to-treat cancers based on a variety of experimental platforms; Aim 3 is to conduct innovative clinical interventions which will affect the course of the disease and the well-being of patients. The Program has 20 members from 12 different departments or sections. Annual extramural funding of program members was ~ $253,000 per member. Among the members' 53 publications, 34% were intra-programmatic, 32% were inter-programmatic, and 51% were inter-institutional, demonstrating the collaborative spirit and national and international stature of the Program?s research and investigators.